Bielecki B, Mazurek A, Wolinski P, Glabinski A
Department of Experimental and Clinical Neurology, Medical University of Lodz, Lodz, Poland.
Scand J Immunol. 2007 Oct;66(4):383-92. doi: 10.1111/j.1365-3083.2007.01954.x.
Chemokines and their receptors are important players in organism homeostasis, development and immune response to inflammatory stimuli. It has been recently confirmed that they are also involved in the development of several autoimmune diseases. In this study, we analysed the expression of two recently identified CC chemokine receptors, CCR7 and CCR8, in the central nervous system (CNS) and in peripheral tissues during chronic relapsing experimental autoimmune encephalomyelitis (ChREAE) -- an animal model of the human demyelinating disease multiple sclerosis (MS). We observed upregulation of both chemokine receptors in the CNS during the first and second attacks of ChREAE, whereas disease remission was characterized by a lower expression of those receptors. An analysis of the kinetics of CCR7 and CCR8 expression in the CNS during the first attack of the disease showed a constant increase in the first few days after the onset of clinical signs. This expression correlated with the clinical severity of ChREAE. CCR7-positive mononuclear cells were detected mostly in perivascular inflammatory cuffs in the CNS. In peripheral tissues (the spleen and kidneys) expression of both receptors was not upregulated during active ChREAE. These findings suggest that CCR7 and CCR8 may play a significant role in the pathogenesis of EAE and probably MS.
趋化因子及其受体在机体稳态、发育以及对炎症刺激的免疫反应中发挥着重要作用。最近已证实它们也参与了多种自身免疫性疾病的发展。在本研究中，我们分析了两种最近鉴定出的CC趋化因子受体CCR7和CCR8在慢性复发性实验性自身免疫性脑脊髓炎（ChREAE）——人类脱髓鞘疾病多发性硬化症（MS）的动物模型——过程中在中枢神经系统（CNS）和外周组织中的表达。我们观察到在ChREAE的首次和第二次发作期间，中枢神经系统中这两种趋化因子受体均上调，而疾病缓解期的特征是这些受体的表达较低。对疾病首次发作期间中枢神经系统中CCR7和CCR8表达动力学的分析表明，在临床症状出现后的头几天表达持续增加。这种表达与ChREAE的临床严重程度相关。CCR7阳性单核细胞主要在中枢神经系统的血管周围炎性套中检测到。在活跃的ChREAE期间，外周组织（脾脏和肾脏）中这两种受体的表达未上调。这些发现表明CCR7和CCR8可能在EAE以及可能在MS的发病机制中发挥重要作用。
